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Cell Calcium. 1996 Jun;19(6):473-83.

Bcl-2 acts subsequent to and independent of Ca2+ fluxes to inhibit apoptosis in thapsigargin- and glucocorticoid-treated mouse lymphoma cells.

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  • 1Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. cwd@po.cwru.edu

Abstract

The mechanism by which Bcl-2 inhibits apoptosis is unknown. One proposal is that Bcl-2 regulates intracellular Ca2+ fluxes thought to mediate apoptosis. In the present study, we investigated Bcl-2's mechanism of action by determining the effect of Bcl-2 on intracellular Ca2+ fluxes in the WEHI7.2 mouse lymphoma cell line, which does not express Bcl-2, and its stable transfectant, W.Hb12, which expresses a high level of Bcl-2. Treatment with the endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin produced marked alterations in intracellular Ca2+ homeostasis in both WEHI7.2 and W.Hb12 cells, including elevation of free cytosolic Ca2+, endoplasmic reticulum Ca2+ pool depletion, capacitative entry of extracellular Ca2+, and increased loading of Ca2+ into mitochondria. Similar changes in intracellular Ca2+ occurred spontaneously in both cell lines following exponential growth. In both situations, W.Hb12 cells maintained optimal viability despite marked alterations in intracellular Ca2+, whereas WEHI7.2 cells underwent apoptosis. Treatment with the glucocorticoid hormone, dexamethasone, induced apoptosis in WEHI7.2 cells, but not in W.HB12 cells, even though dexamethasone treatment did not alter intracellular Ca2+ homeostasis in either cell line. These findings indicate that Bcl-2 acts downstream from intracellular Ca2+ fluxes in a pathway where Ca(2+)-dependent and Ca(2+)-independent death signals converge.

PMID:
8842514
[PubMed - indexed for MEDLINE]
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